. Chou and Wagner will co-direct this Core to serve the following roles in the Center. 1. Provide support in NMR spectroscopy. NMR pulse sequences get increasingly sophisticated, and often only a few specialists can set up the complicated experiments properly. In particular, for challenging systems such as 30 kDa MPs in complex with detergent micelles, the difference between optimized and un-optimized NMR pulse sequence could be the difference between feasible and not feasible project. Therefore, this Core will first optimize the existing NMR pulse sequences and their corresponding hardware parameter set for immediate application in the pipeline. These sequences include standard 3D experiments for assignment of backbone and sidechain resonances, and for NOE and RDC measurements. While there are many different ways to implement these experiments, this Core will tailor the experiments for a 30 kDa helical MP with MP-specific considerations such as suppression of detergent signals and resonance overlap and heterogeneity. The Core will then perform thorough test on NMR experiments to be developed in the Projects, e.g., the non-uniformly sampled (NUS) 4D NOESYs, before distribution to the scientific community. In addition to the planned compilation of NMR pulse experiments, the Core will assist the components of the Center in designing new specialized NMR experiments to solve ad hoc spectroscopic problem. The above duties will be performed by Dr. Hari Arthanari and Dr. Kirill Oxenoid, who have been assisting people in the Wagner and Chou lab in designing NMR pulse schemes and in setting up NMR experiments for the past 5 years. 2. Provide support in computation. With the development of NUS 4D experiments, data processing becomes challenging and computation intensive. For example, processing a NUS 4D NOESY with specialized program will takes about two weeks on a modern computer. Dr. Sven Hybert has been developing new methods for processing NUS NMR data (Hyberts et al., 2009). He will develop tools for processing NUS 4D NOESYs and assist other members of the Center in processing and analyzing NMR spectra. This Core will also provide support in structure calculation. Dr. Marcelo Berardi will thoroughly test existing and develop new protocols for structure calculation. He has been developing a program for determining backbone dihedral angles of the target MPs using a PDB-wide RDC-based molecular fragment replacement (MFR) approach. He will also be responsible for assisting members of the Center in all aspects of structure calculation and refinement. 3. Provide computation infrastructure and dissemination. A good computation infrastructure is key to the success of the Center as NMR data analysis and structure calculation are both very computation intensive. Dr. Piotr Sliz, the director of the Structural Biology Grid (SBGrid), will manage computation resource for the Center, including network file system, data storage, and CPU clusters. SBGrid provide computational support to more than 100 structural biology labs across the United States (www.sbgrid.org);it maintains a package of the most up-to-date software in X-ray, NMR, and EM and synchronizes them with these labs. It also provides these labs with technical support in structure calculation and refinement. Therefore, SBGrid is an established medium for disseminating the knowledge and tools from the Center. Dr. Ian Stokes-Rees is an expert in grid technologies, and before joining SBGrid worked on grid projects at the European Organization for Nuclear Research (CERN). He will construct clusters and implement parallel processing for the computationally intensive tasks such as MFR and 4D spectrum reconstruction. He will also assist the members of the Center to simultaneously utilize over 50,000 CPUs around the world through the Open Science Grid organization. 4. Maintenance of NMR instruments. Gregory Heffron, the current NMR facility manager at Harvard Medical School, will maintain and upgrade NMR spectrometers to meet the spectrometer needs of the Center. 7.4. RESOURCES. The Center will have access to three 500 MHz, three 600 MHz, one 750 MHz, one 800 MHz, and a half of 900 MHz spectrometers, all equipped with cryogenic probes. The Center will have access to a 128 CPU cluster, and a 108 core Mac OS X cluster.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZGM1-CBB-3)
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Harvard University
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Yang, Qin; Bruschweiler, Sven; Chou, James J (2014) A self-sequestered calmodulin-like Caýýýýý sensor of mitochondrial SCaMC carrier and its implication to Caýýýýý-dependent ATP-Mg/P(i) transport. Structure 22:209-17
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